Long-term follow-up of a supradescemetic keratoprosthesis in rabbits: an immunofluorescence study

  • Edgar M. Espana
  • Ana C. Acosta
  • Josef Stoiber
  • Viviana Fernandez
  • Peggy D. Lamar
  • Franck L. Villain
  • Emmanuel Lacombe
  • Eduardo Alfonso
  • Jean-Marie Parel
Cornea
First Online:
Received:
Revised:
Accepted:

Abstract

Objective

To evaluate the long-term clinical and immunohistological outcome of two different non-penetrating keratoprosthesis (KPro) implanted in non-injured rabbit corneas.

Materials and methods

Three rabbits underwent implantation of a pHEMA-MMA34 synthetic cornea in the supradescemetic space, and PMMA synthetic corneas in the supradescemetic space and within the central stroma. Animals were followed for at least 24 months before euthanasia. Periodic evaluation was performed with slit-lamp examination and photography. At the end of the follow-up, histological examination including hematoxylin eosin staining and immunocharacterization against collagen IV, alpha smooth muscle actin (α-SMA) and macrophages was performed.

Results

The pHEMA-MMA34 implant was not extruded, and remained transparent until the end of follow-up. This material did not induce any cell infiltration, corneal scarring or tissue remodeling in the surrounding stroma as shown by immunofluorescence. In contrast, synthetic corneas made of PMMA-induced myofibroblast differentiation, stromal remodeling and macrophage infiltration. This reaction was even more significant in the rabbit with the PMMA implant within the corneal stroma.

Conclusion

pHEMA-MMA34 was clinically biocompatible, and did not induce any inflammatory reaction or scarring when implanted in the supradescemetic space. This material showed more promising biocompatibility results than for PMMA, whether implanted within the central cornea stroma or in the supradescemetic space.

Keywords

Keratoprosthesis Rabbits Myofibroblasts Keratocytes Biomaterials 
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Notes

Acknowledgements

Professor Francisco Fantes provided invaluable clinical insights.

Supported by

Florida Lions Eye Bank; European Project BMH4-CT97-9507; FWF Austrian Science Fund; Corneal SA Paris, France; NIH center Grant P30-EY014801; Research to Prevent Blindness; Henri and Flore Lesieur Foundation.

References

  1. 1.
    Castroviejo R, Cardona H, DeVoe AG (1969) The present status of prosthokeratoplasty. Trans Am Ophthalmol Soc 67:207–234PubMedGoogle Scholar
  2. 2.
    Cardona H, DeVoe AG (1977) Prosthokeratoplasty. Trans Am Acad Ophthalmol Otolaryngol 83:271–280Google Scholar
  3. 3.
    Hicks CR, Fitton JH, Chirila TV, Crawford GJ, Constable IJ (1997) Keratoprostheses: advancing toward a true artificial cornea. Surv Ophthalmol 42:175–189CrossRefPubMedGoogle Scholar
  4. 4.
    Khan B, Dudenhoefer EJ, Dohlman CH (2001) Keratoprosthesis: an update. Curr Opin Ophthalmol 12:282–287CrossRefPubMedGoogle Scholar
  5. 5.
    Parel JM, Sweeney D (2005) OOKP. Cornea 24:893–894CrossRefPubMedGoogle Scholar
  6. 6.
    Falcinelli G, Falsini B, Taloni M, Colliardo P, Falcinelli G (2005) Modified osteo-odonto-keratoprosthesis for treatment of corneal blindness: long-term anatomical and functional outcomes in 181 cases. Arch Ophthalmol 123:1319–1329CrossRefPubMedGoogle Scholar
  7. 7.
    Helena MC, Baerveldt F, Kim W-J, Wilson SE (1998) Keratocyte apoptosis after corneal surgery. Invest Ophthalmol Vis Sci 39:276–283PubMedGoogle Scholar
  8. 8.
    Jester JV, Petroll WM, Cavanagh HD (1999) Corneal stromal wound healing in refractive surgery: the role of myofibroblasts. Prog Retin Eye Res 18:311–356CrossRefPubMedGoogle Scholar
  9. 9.
    Wilson SE, Kim W-J (1998) Keratocyte apoptosis: implications on corneal wound healing, tissue organization, and disease. Invest Ophthalmol Vis Sci 59:220–226Google Scholar
  10. 10.
    Wilson SE, Mohan RR, Mohan RR, Ambrósio R Jr, Hong J, Lee J (2001) The corneal wound healing response: cytokine-mediated interaction of the epithelium, stroma, and inflammatory cells. Prog Retin Eye Res 20:625–637CrossRefPubMedGoogle Scholar
  11. 11.
    Mohan RR, Hutcheon AE, Choi R, Hong J, Lee J, Mohan RR, Ambrósio R Jr, Zieske JD, Wilson SE (2003) Apoptosis, necrosis, proliferation, and myofibroblast generation in the stroma following LASIK and PRK. Exp Eye Res 76:71–87CrossRefPubMedGoogle Scholar
  12. 12.
    Jester JV, Petroll WM, Barry PA, Cavanagh HD (1995) Expression of α-smooth muscle (a-SM) actin during corneal stromal wound healing. Invest Ophthalmol Vis Sci 36:809–819PubMedGoogle Scholar
  13. 13.
    Funderburgh JL, Funderburgh ML, Mann MM, Corpuz L, Roth MR (2001) Proteoglycan expression during transforming growth factor beta-induced keratocyte–myofibroblast transdifferentiation. J Biol Chem 276:44173–44178CrossRefGoogle Scholar
  14. 14.
    Funderburgh JL, Funderburgh ML, Mann MM, Prakash S, Conrad GW (1996) Synthesis of corneal keratan sulfate proteoglycans by bovine keratocytes in vitro. J Biol Chem 271:31431–31436CrossRefGoogle Scholar
  15. 15.
    León CR, Barraquer JI Jr, Barraquer JI (1997) Coralline hydrdoxyapatite keratoprosthesis in rabbits. J Refract Surg 13:74–78PubMedGoogle Scholar
  16. 16.
    Caldwell DR (1997) The soft keratoprosthesis. Trans Am Ophthalmol Soc 95:751–802PubMedGoogle Scholar
  17. 17.
    Pintucci S, Perilli R, Formisano G, Caiazza S (2001) Influence of dacron tissue thickness on the performance of the Pintucci biointegrable keratoprosthesis: an in vitro and in vivo study. Cornea 20:647–650CrossRefPubMedGoogle Scholar
  18. 18.
    Stoiber J, Fernandez V, Kaminski S, Lamar PD, Dubovy S, Alfonso E, Parel JM (2004) Biological response to a supradescemetic synthetic cornea in rabbits. Arch Ophthalmol 122:1850–1855CrossRefPubMedGoogle Scholar
  19. 19.
    Stoiber J, Fernandez V, Lamar PD, Kaminski S, Acosta AC, Dubovy S, Alfonso E, Parel JM (2005) Biocompatibility of a nonpenetrating synthetic cornea in vascularized rabbit corneas. Cornea 24:467–473CrossRefPubMedGoogle Scholar
  20. 20.
    Ishizaki M, Shimoda M, Wakamatsu K, Ogro T, Yamanaka N, Kao CW, Kao WW (1997) Stromal fibroblasts are associated with collagen IV in scar tissues of alkali-burned and lacerated corneas. Curr Eye Res 16:339–348CrossRefPubMedGoogle Scholar
  21. 21.
    Espana EM, Ti SE, Grueterich M, Touhami A, Tseng SC (2003) Corneal stromal changes following reconstruction by ex vivo expanded limbal epithelial cells in rabbits with total limbal stem cell deficiency. Br J Ophthalmol 87:1509–1514CrossRefPubMedGoogle Scholar
  22. 22.
    Jester JV, Barry-Lane PA, Cavanagh HD, Petroll WM (1996) Induction of α-smooth muscle actin expression and myofibroblast transformation in cultured corneal keratocytes. Cornea 15:505–516CrossRefPubMedGoogle Scholar
  23. 23.
    Parel J-M, Kaminski S, Fernandez V, Alfonso E, Lamar P, Lacombe E, Duchesne B, Dubovy S, Manns F, Rol PO (2002) Synthetic cornea: biocompatibility and optics. In: Manns F, Söderberg PG, Ho A (eds) Ophthalmic Technologies XII. SPIE Proc 4611:123–128Google Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Edgar M. Espana
    • 1
  • Ana C. Acosta
    • 1
  • Josef Stoiber
    • 1
    • 2
  • Viviana Fernandez
    • 1
  • Peggy D. Lamar
    • 1
  • Franck L. Villain
    • 1
    • 5
  • Emmanuel Lacombe
    • 1
    • 6
  • Eduardo Alfonso
    • 1
  • Jean-Marie Parel
    • 1
    • 3
    • 4
  1. 1.Ophthalmic Biophysics Center, Bascom Palmer Eye InstituteUniversity of Miami Miller School of MedicineMiamiUSA
  2. 2.Department of Ophthalmology and OptometryParacelsus Private Medical UniversitySalzburgAustria
  3. 3.Department of Biomedical EngineeringUniversity of Miami College of EngineeringMiamiUSA
  4. 4.CHU Sart–TilmanUniversity of LiègeLiègeBelgium
  5. 5.Corneal SA/Croma Pharma SAParisFrance
  6. 6.Hospital Leopold BellanParisFrance

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